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The anticancer efficacy of two different classes of NSAIDs, the nonspecific cyclooxygenase (COX) inhibitor aspirin and the specific COX-2 inhibitor celecoxib, was examined at their therapeutic anti-inflammatory doses during 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in a rat model. Eight to 10-week-old male rats of Sprague strain were divided into four groups. While group 1 served as control and received the vehicle of the drugs, groups 2, 3, and 4 were administered freshly prepared DMH in 1 mM EDTA saline (pH 7.0) (30 mg/kg body weight/week, subcutaneously). Groups 3 and 4 were also given a daily treatment of aspirin (60 mg/kg body weight, orally) and celecoxib (6 mg/kg body weight, orally), respectively, both prepared in carboxy-methyl cellulose. Animals were sacrificed at the end of 12 weeks and colons from different groups were subjected to macroscopic and histopathological studies, enzymatic activities of superoxide dismutase (SOD) and catalase (CAT), and determination of lipid peroxide level. The maximum number of raised mucosal lesions in proximal, middle, and distal regions of the colon was found in the DMH group alone, and the lowest number was found in the celecoxib-treated DMH group. Histological studies also showed the highest occurrence of dysplastic aberrant crypt foci (ACF) associated with enlarged lymphoid follicles in all the three portions of colon (i.e., proximal, middle, and distal). The aspirin-administered DMH group had lesser ACF in the proximal and middle portions and no ACF in the distal region. The celecoxib-administered DMH group showed no ACF in the middle region of the rat colon. DMH treatment induced lipid peroxidation and inhibited the activities of SOD and CAT. Both the aspirin- and celecoxib-treated DMH groups showed a marked lowering of the lipid peroxide level along with a significant enhancement of CAT activity when compared with the DMH-treated group. The results show that celecoxib was found to be more effective in reducing the ACF occurrence and aggregates of lymphoid tissue than the nonselective COX inhibitor aspirin, and suggests a possible chemoprevention modality in colon cancer. This may have important implications as COX-2 selective drugs at anti-inflammatory doses are better tolerated clinically than standard NSAIDs, thus making them potentially better chemopreventive agents in colon cancer. [ABSTRACT FROM AUTHOR]

Monensin, a carboxylic ionophore, is well known for Na + /H + exchanger activity across biological membranes. It is also used in the poultry industry for its useful effects as a food additive. The present study has been designed to investigate the effects of monensin on some oxidative stress-related parameters in rat testis. Monensin was administered intratesticularly (5 μg/testis) to both testes by a single dose to Wistar rats for different time periods. After the completion of the respective treatments, various parameters reflecting the antioxidant defense system of the tissue were monitored and marked changes were found in the activities of various enzymes as well as in the levels of reduced glutathione and lipid peroxidation. After 1, 2, 3, and 4 days of monensin treatment, the activity of superoxide dismutase was found to be unaltered. However, after 2 days of monensin treatment, glutathione-S-transferase and catalase showed inhibition in their activities along with the depletion of glutathione (reduced) accompanied by a marked increase in lipid peroxidation. The increase in lipid peroxidation was noticeable even after 1 day of monensin administration. The inhibition in glutathione-S-transferase and glutathione peroxidase activities was also observed along with an increase in lipid peroxidation at the end of the 3-day posttreatment period, while, the 4-day posttreatment schedule caused an increase in the activity of glutathione reductase and glutathione peroxidase that was also accompanied by an inhibition of catalase. The findings of the present study are indicative of the potential of monensin in testicular tissue in contraceptive intervention. [ABSTRACT FROM AUTHOR]